tbuckley/cabot-search huggingface dataset:
Cholera is back but the world is looking away
Authors: Petra Khoury
Journal: BMJ (2023)

and tackle humanitarian crises at cholera's roots, says Petra Khoury Petra Khoury director of the Health and Care department Once thought to be close to eradication, cholera is back-dehydrating and killing people within hours and ravaging communities across six continents.Despite the alarming numbers of cases and deaths over the past year, decision makers are averting their eyes, leaving people to die from a preventable and treatable disease.The healthcare community should sound the alarm for immediate actions.A strong and global emergency response is urgently needed, but it is only a first step.More than ever the world must invest in water and sanitation systems and prepare communities before outbreaks occur.
How we treat primary immune thrombocytopenia in adults
Authors: Xin-guang Liu, Yu Hou, Ming Hou
Journal: Journal of Hematology & Oncology (2023)

Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple humoral and cellular immune abnormalities result in accelerated platelet destruction and suppressed platelet production in ITP. The diagnosis remains a clinical exclusion of other causes of thrombocytopenia. Treatment is not required except for patients with active bleeding, severe thrombocytopenia, or cases in need of invasive procedures. Corticosteroids, intravenous immunoglobulin, and anti-RhD immunoglobulin are the classical initial treatments for newly diagnosed ITP in adults, but these agents generally cannot induce a long-term response in most patients. Subsequent treatments for patients who fail the initial therapy include thrombopoietic agents, rituximab, fostamatinib, splenectomy, and several older immunosuppressive agents. Other potential therapeutic agents, such as inhibitors of Bruton's tyrosine kinase and neonatal Fc receptor, are currently under clinical evaluation. An optimized treatment strategy should aim at elevating the platelet counts to a safety level with minimal toxicity and improving patient health-related quality of life, and always needs to be tailored to the patients and disease phases. In this review, we address the concepts of adult ITP diagnosis and management and provide a comprehensive overview of current therapeutic strategies under general and specific situations.
Accounting for cis-regulatory constraint prioritizes genes likely to affect species-specific traits
Authors: Alexander L. Starr, David Gokhman, Hunter B. Fraser
Journal: Genome biology (2023)

Abstract Measuring allele-specific expression in interspecies hybrids is a powerful way to detect cis- regulatory changes underlying adaptation. However, it remains difficult to identify genes most likely to explain species-specific traits. Here, we outline a simple strategy that leverages population-scale allele-specific RNA-seq data to identify genes that show constrained cis- regulation within species yet show divergence between species. Applying this strategy to data from human-chimpanzee hybrid cortical organoids, we identify signatures of lineage-specific selection on genes related to saccharide metabolism, neurodegeneration, and primary cilia. We also highlight cis- regulatory divergence in CUX1 and EDNRB that may shape the trajectory of human brain development.
Myeloid Maturity: ATRA to Enhance Anti–PD-1?
Authors: Daniel J. Olson, Jason J. Luke
Journal: Clinical Cancer Research (2023)

Summary Myeloid-derived suppressor cells (MDSC) are associated with resistance to anti-PD-1 therapies. All-trans retinoic acid (ATRA) may induce maturation of MDSCs and alter their immunosuppressive effects. Adding ATRA to pembrolizumab may target this resistance mechanism to enhance the overall impact of anti-PD-1–based immunotherapy. See related article by Tobin et al., p. 1209
Rising to the challenge – 2023<i>BJSM</i>–AMSSM collaborative special issue
Authors: Jason L Zaremski, Dusty Marie Narducci
Journal: British Journal of Sports Medicine (2023)

Three years after the COVID-19 pandemic upended life across the globe, sports and exercise medicine (SEM) clinicians have shown resilience, strength, creativity and motivation to face the long-term societal, economic and cultural challenges from the pandemic.As we embrace a new 'normal', it is with extreme pleasure that the British Journal of Sports Medicine (BJSM) and the American Medical Society for Sports Medicine (AMSSM) present the 2023 BJSM-AMSSM collaborative issue.Our goal in developing this issue is to complement the annual AMSSM meeting and share some of the outstanding work from US and international experts.this work.
Liquid biopsy approaches to capture tumor evolution and clinical outcomes during cancer immunotherapy
Authors: Lavanya Sivapalan, Joseph C Murray, Jenna VanLiere Canzoniero, Blair Landon, Jennifer Jackson, Susan Scott, Vincent Lam, Benjamin P. Levy, Mark Sausen, Valsamo Anagnostou
Journal: Journal for ImmunoTherapy of Cancer (2023)

Circulating cell-free tumor DNA (ctDNA) can serve as a real-time biomarker of tumor burden and provide unique insights into the evolving molecular landscape of cancers under the selective pressure of immunotherapy. Tracking the landscape of genomic alterations detected in ctDNA may reveal the clonal architecture of the metastatic cascade and thus improve our understanding of the molecular wiring of therapeutic responses. While liquid biopsies may provide a rapid and accurate evaluation of tumor burden dynamics during immunotherapy, the complexity of antitumor immune responses is not fully captured through single-feature ctDNA analyses. This underscores a need for integrative studies modeling the tumor and the immune compartment to understand the kinetics of tumor clearance in association with the quality of antitumor immune responses. Clinical applications of ctDNA testing in patients treated with immune checkpoint inhibitors have shown both predictive and prognostic value through the detection of genomic biomarkers, such as tumor mutational burden and microsatellite instability, as well as allowing for real-time monitoring of circulating tumor burden and the assessment of early on-therapy responses. These efforts highlight the emerging role of liquid biopsies in selecting patients for cancer immunotherapy, monitoring therapeutic efficacy, determining the optimal duration of treatment and ultimately guiding treatment selection and sequencing. The clinical translation of liquid biopsies is propelled by the increasing number of ctDNA-directed interventional clinical trials in the immuno-oncology space, signifying a critical step towards implementation of liquid biopsies in precision immuno-oncology.
Pan-3D genome analysis reveals structural and functional differentiation of soybean genomes
Authors: Lingbin Ni, Yucheng Liu, Xin Ma, Tengfei Liu, Xiaoyue Yang, Zhao Wang, Qianjin Liang, Shulin Liu, Min Zhang, Zheng Wang, Yanting Shen, Zhixi Tian
Journal: Genome biology (2023)

Abstract Background High-order chromatin structure plays important roles in gene regulation. However, the diversity of the three-dimensional (3D) genome across plant accessions are seldom reported. Results Here, we perform the pan-3D genome analysis using Hi-C sequencing data from 27 soybean accessions and comprehensively investigate the relationships between 3D genomic variations and structural variations (SVs) as well as gene expression. We find that intersection regions between A/B compartments largely contribute to compartment divergence. Topologically associating domain (TAD) boundaries in A compartments exhibit significantly higher density compared to those in B compartments. Pan-3D genome analysis shows that core TAD boundaries have the highest transcription start site (TSS) density and lowest GC content and repeat percentage. Further investigation shows that non-long terminal repeat (non-LTR) retrotransposons play important roles in maintaining TAD boundaries, while Gypsy elements and satellite repeats are associated with private TAD boundaries. Moreover, presence and absence variation (PAV) is found to be the major contributor to 3D genome variations. Nevertheless, approximately 55% of 3D genome variations are not associated with obvious genetic variations, and half of them affect the flanking gene expression. In addition, we find that the 3D genome may also undergo selection during soybean domestication. Conclusion Our study sheds light on the role of 3D genomes in plant genetic diversity and provides a valuable resource for studying gene regulation and genome evolution.
Racial Health Equity and Social Needs Interventions
Authors: Crystal W. Cené, Meera Viswanathan, Caroline M. Fichtenberg, Nila A. Sathe, Sara M. Kennedy, Laura M. Gottlieb, Yuri Cartier, Monica E. Peek
Journal: JAMA Network Open (2023)

Social needs interventions aim to improve health outcomes and mitigate inequities by addressing health-related social needs, such as lack of transportation or food insecurity. However, it is not clear whether these studies are reducing racial or ethnic inequities.
TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?
Authors: Karolina Solhusløkk Höse, Adam Stenman, Fredrika Svahn, Catharina Larsson, C. Christofer Juhlin
Journal: Endocrine Pathology (2023)

Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells. Even though only 10-15% of the tumors metastasize, all PPGLs are considered potentially malignant. Topoisomerase 2A (TOP2A) is a protein involved in cell proliferation and has been found to be over-expressed in metastatic PPGL. To provide support whether TOP2A could serve as a prognostic marker, 88 PPGLs (of which 8 metastatic/relapsing) and 10 normal adrenal gland samples were assessed for TOP2A mRNA expression using quantitative real-time PCR (qRT-PCR) and TOP2A immunohistochemistry. Comparisons to clinical parameters connected to metastatic behavior were made, and The Cancer Genome Atlas was used for validation of the results. A significant association between high TOP2A mRNA expression in primary PPGL and subsequent metastatic events (p = 0.008) was found, as well as to specific histological features and clinical parameters connected to metastatic behavior and mutations in SDHB. TOP2A immunoreactivity was calculated as an index of positive nuclei divided by the total amount of nuclei, and this index associated with TOP2A mRNA levels (p = 0.023) as well as the Ki-67 labeling index (p = 0.001). To conclude, TOP2A is a potential prognostic marker as it is frequently elevated in PPGL displaying subsequent metastatic disease, and future studies in larger cohorts are warranted to determine if a TOP2A index as assessed by immunohistochemistry could be a marker of poor outcome. Additionally, elevated levels of TOP2A could indicate a potential actionable event, and future studies with topoisomerase inhibitors would be of interest.
Patient-Reported Outcome Measures in Oncology Drugs Approved by the European Medicines Agency, 2017-2021
Authors: Oriana Ciani, Michela Meregaglia, Francesco De Lorenzo, Francesco Perrone, Carmine Pinto
Journal: JAMA Network Open (2023)

This cross-sectional study investigates the use of patient-reported outcome measures in new marketing authorizations for oncology drugs approved by the European Medicines Agency (EMA) between 2017 and 2021.
Tight Glycemic Control, Inflammation, and the ICU: Evidence for Heterogeneous Treatment Effects in Two Randomized Controlled Trials
Authors: Matt S. Zinter, Daniela Markovic, Lisa A. Asaro, Vinay M. Nadkarni, Patrick S. McQuillen, Pratik Sinha, Michael A. Matthay, Marc G. Jeschke, Michael S. D. Agus, Anil Sapru, Michael Agus, Kerry Coughlin-Wells, Kyle Hughes, Jaclyn French, Meghan Fitzgerald, Vijay Srinivasan, Martha Sisko, Ranjit S. Chima, Kelli Howard, Rhonda Jones, Neal J Thomas, Debbie Spear, Simon Li, Alan Pinto, Peter Eldridge, Christopher Newth, Jeni Kwok, Amanda B Hassinger, Haiping Qiao, Kris Bysani, Tracey Monjure, Edward Vincent Faustino, Joana Tala, Sarah A Kandil, Tyler Quinn, Eliotte Hirshberg, Jennifer Lilley, Kupper Wintergerst, Janice E Sullivan, Kristen Lee, Adam Schwarz, Cathy Flores, Ofelia Vargas-Shiraishi, Lauren Sorce, Lauren Marsillio, Avani Shukla, Natalie Cvijanovich, Heidi Flori, Becky Brumfield, Cheryl Stone, Mary Dahmer, Chaandini Jayachandran, Myke Federman, Kayley Wong, Sitaram S Vangala, Matteo Pellegrini, Brunilda Balliu, Kinisha P Gala, Theresa Kirkpatrick, Tanaya Deshmukh, Manvita Mareboina, Nguyen Do, Neda Ashtari, Anna Ratiu, Sholeen Nett, Marcy Singleton, Dean Jarvis, Mary McNally, Karlyn Martini, Neethi Pinto, Grace Chong, Chiara Rodgers, Shirley Viteri, Ramany John, Teresa Mulholland, Gwen Pellicciotti, Anil Sapru, Patrick McQuillen, Matt Zinter, Shrey Goel, Mustafa Alkhouli, Anne McKenzie, Denise Villarreal-Chico
Journal: American Journal of Respiratory and Critical Care Medicine (2023)
Malignant Neoplasms of the Gastrointestinal Tract After Blood or Marrow Transplant
Authors: Andrew McDonald, Chen Dai, Qingrui Meng, Lindsey Hageman, Joshua Richman, Jessica Wu, Liton Francisco, Elizabeth Ross, Nora Balas, Alysia Bosworth, Hok Sreng Te, F. Lennie Wong, Wendy Landier, Donna Salzman, Ravi Bhatia, Daniel J. Weisdorf, Stephen J. Forman, Saro H. Armenian, Smita Bhatia
Journal: JAMA Oncology (2023)

Survivors of blood or marrow transplant (BMT) are at increased risk of subsequent malignant neoplasms (SMNs). Cancers of the gastrointestinal (GI) system are of special interest because their clinical behavior is often aggressive, necessitating early detection by increasing awareness of high-risk populations.
Clinicians’ and Researchers’ Perspectives on a New Chronic Obstructive Pulmonary Disease Exacerbation Definition: Rome Wasn’t Built in a Day
Authors: Malik A. Althobiani, Amar J. Shah, Bilal Khan, John R. Hurst
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Clinicians' and Researchers' Perspectives on a New COPD Exacerbation Definition: Rome Wasn't Built in a Day." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Epidemiology of Human Mpox — Worldwide, 2018–2021
Authors: Andrea M. McCollum, Victoria Shelus, Alexandra Hill, Tieble Traore, Bernard Onoja, Yoshinori Nakazawa, Jeffrey B. Doty, Adesola Yinka-Ogunleye, Brett W. Petersen, Christina L. Hutson, Rosamund Lewis
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Monkeypox (mpox) is a zoonotic disease caused by Monkeypox virus (MPXV), an Orthopoxvirus; the wild mammalian reservoir species is not known. There are two genetic clades of MPXV: clade I and clade II (historically found in central and west Africa, respectively), with only Cameroon reporting both clades (1). Human cases have historically been reported from 1) mostly rural, forested areas in some central and west African countries; 2) countries reporting cases related to population migration or travel of infected persons; and 3) exposure to imported infected mammals (2). The annual number of cases in Africa has risen since 2014 and cumulatively surpassed reports from the previous 40 years for most countries. This reemergence of mpox might be due to a combination of environmental and ecological changes, animal or human movement, the cessation of routine smallpox vaccination since its eradication in 1980, improvements in disease detection and diagnosis, and genetic changes in the virus (2). This report describes the epidemiology of mpox since 1970 and during 2018-2021, using data from national surveillance programs, World Health Organization (WHO) bulletins, and case reports, and addresses current diagnostic and treatment challenges in countries with endemic disease. During 2018-2021, human cases were recognized and confirmed in six African countries, with most detected in the Democratic Republic of the Congo (DRC) and Nigeria. The reemergence and increase in cases resulted in its being listed in 2019 as a priority disease for immediate and routine reporting through the Integrated Disease Surveillance and Response strategy in the WHO African region.* In eight instances, patients with mpox were identified in four countries outside of Africa after travel from Nigeria. Since 2018, introductory and intermediate training courses on prevention and control of mpox for public health and health care providers have been available online at OpenWHO.†,§ The global outbreak that began in May 2022¶ has further highlighted the need for improvements in laboratory-based surveillance and access to treatments and vaccines to prevent and contain the infection, including in areas of Africa with endemic mpox.
Comparison of Screening Mammogram Rates Before vs During the COVID-19 Pandemic Among Medicaid Beneficiaries in Louisiana
Authors: Yixue Shao, Kevin Callison, Andrew Anderson, Thomas A. LaVeist, Brigham Walker
Journal: JAMA Network Open (2023)

This cohort study investigates differences in screening mammography before vs during the COVID-19 pandemic by race and ethnicity among Medicaid beneficiaries in Louisiana.
Emergency Department Visits Among Patients With Cancer in the US
Authors: Erek S. Majka, N. Seth Trueger
Journal: JAMA Network Open (2023)

Amir Alishahi Tabriz, MD, PhD, MPH; Kea Turner, PhD, MPH, MA; Young-Rock Hong, PhD, MPH; Sara Gheytasvand, MD; Benjamin D. Powers, MD, MS; Jennifer Elston Lafata, PhD
Acetyl-CoA metabolism in cancer
Authors: David A. Guertin, Kathryn E. Wellen
Journal: Nature reviews. Cancer (2023)

Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle and is the essential building block for fatty acid and isoprenoid biosynthesis. It also functions as a signalling metabolite as the substrate for lysine acetylation reactions, enabling the modulation of protein functions in response to acetyl-CoA availability. Recent years have seen exciting advances in our understanding of acetyl-CoA metabolism in normal physiology and in cancer, buoyed by new mouse models, in vivo stable-isotope tracing approaches and improved methods for measuring acetyl-CoA, including in specific subcellular compartments. Efforts to target acetyl-CoA metabolic enzymes are also advancing, with one therapeutic agent targeting acetyl-CoA synthesis receiving approval from the US Food and Drug Administration. In this Review, we give an overview of the regulation and cancer relevance of major metabolic pathways in which acetyl-CoA participates. We further discuss recent advances in understanding acetyl-CoA metabolism in normal tissues and tumours and the potential for targeting these pathways therapeutically. We conclude with a commentary on emerging nodes of acetyl-CoA metabolism that may impact cancer biology.
Obstetric, neonatal, and child health outcomes following embryo biopsy for preimplantation genetic testing
Authors: Alessandra Alteri, Greta Chiara Cermisoni, Mirko Pozzoni, Gerarda Gaeta, Paolo Ivo Cavoretto, Paola Viganò
Journal: Human Reproduction Update (2023)

Abstract BACKGROUND Preimplantation genetic testing (PGT) of embryos developed in vitro requires a biopsy for obtaining cellular samples for the analysis. Signs of cell injury have been described in association with this procedure. Thus, the consequences of the biopsy on obstetric and neonatal outcomes have been the subject of some quantitative analyses, although the reliability of data pooling may be limited by important issues in the various reports. OBJECTIVE AND RATIONALE The present review identifies evidence for whether pregnancies conceived after embryo biopsy are associated with a higher risk of adverse obstetric, neonatal, and long-term outcomes. Available evidence has been summarized considering manipulation at various stages of embryo development. SEARCH METHODS We used the scoping review methodology. Searches of article databases were performed with keywords pertaining to the embryo biopsy technique and obstetric, neonatal, and postnatal outcomes. Studies in which embryos were biopsied at different stages (i.e. both at the cleavage and blastocyst stages) were excluded. We included data on fresh and frozen embryo transfers. The final sample of 31 documents was subjected to qualitative thematic analysis. OUTCOMES Sound evidence is lacking to fully address the issues on the potential obstetric, neonatal or long-term consequences of embryo biopsy. For polar body biopsy, the literature is too scant to draw any conclusion. Some data, although limited and controversial, suggest a possible association of embryo biopsy at the cleavage stage with an increased risk of low birthweight and small for gestational age neonates compared to babies derived from non-biopsied embryos. An increase in preterm deliveries and birth defects in cases of trophectoderm biopsy was suggested. For both biopsy methods (at the cleavage and blastocyst stages), an increased risk for hypertensive disorders of pregnancy was found. However, these findings may be explained by confounders such as other embryo manipulation procedures or by intrinsic patient or population characteristics. WIDER IMPLICATIONS Since there is inadequate evidence to assess obstetric, neonatal, and long-term health outcomes following embryo biopsy, an invasive PGT strategy should be developed with a cautious approach. A non-invasive approach, based on the analysis of embryo cell-free DNA, needs to be pursued to overcome the potential limitations of embryo biopsy.
Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors
Authors: Anne W. J. Martens, Inga Kavazović, Mia Krapić, Su Min Pack, Ramon Arens, Aldo Jongejan, Perry D. Moerland, Eric Eldering, Gerritje J. W. van der Windt, Felix M. Wensveen, Fleur S. Peters, Arnon P. Kater
Journal: Leukemia (2023)
Long-term Trajectories of Physical Function Decline in Women With and Without Cancer
Authors: Elizabeth M. Cespedes Feliciano, Sowmya Vasan, Juhua Luo, Alexandra M. Binder, Rowan T. Chlebowski, Charles Quesenberry, Hailey R. Banack, Bette J. Caan, Electra D. Paskett, Grant R. Williams, Ana Barac, Andrea Z. LaCroix, Ulrike Peters, Kerryn W. Reding, Kathy Pan, Aladdin H. Shadyab, Lihong Qi, Garnet L. Anderson
Journal: JAMA Oncology (2023)

Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical function by cancer site, stage, or treatment compared with cancer-free controls.